[gmx-users] Umbrella sampling for protein-drug system

Justin A. Lemkul jalemkul at vt.edu
Sun Feb 20 19:04:25 CET 2011

Aldo Segura wrote:
> Dear gmx-users,
> I have following the umbrella sampling tutorial at 
> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/umbrella/index.html. 
> I’m trying to use it for a drug-protein system. In the tutorial the 
> group A moves away to group B. I would like to pull the drug to the 
> protein binding-site (i.e., drug move closer to protein). How can I do 
> that? Should I modified the md_pull.mdp file (from the tutorial) 
> changing the value from pull_rate1 (0.01) to a negative value (i.e. 
> -0.01)?  or using pull_geometry   = position and related code instead 
> pull_geometry   = distance?

You may have to make several changes.  Changing the sign of pull_rate1 will 
indeed decrease the COM distance rather than increase it.  Most of the 
pull_geometry values could be useful here, but changing the method may require 
other changes to the pulling settings.  Refer to the manual.

Note that hitting a moving target is substantially harder than inducing a simple 
dissociation of a protein complex, as the tutorial does.  You may be able to 
carefully set a pull_group0 and an appropriate vector along which to pull your 
ligand, but if the protein diffuses or rotates even a small amount (which it 
will), you will likely crash your ligand into some non-target region.  A variety 
of restraints could be used to prevent this from happening, but you may have a 
hard time ensuring that the restraints do not adversely affect the dynamics of 
the binding process.

Probably a more effective approach is to start from a docked complex and pull 
the ligand out.  If you're only looking for a PMF, you can accomplish the same 
results by doing so, and it is substantially easier.


> Thanks in advance,
> *//*
> */=======================================
> Aldo Segura-Cabrera
> Laboratorio de Bioinformática
> Centro de Biotecnología Genómica
> Instituto Politécnico Nacional
> Blvd. Del Maestro esquina Elías Piña, 88710
> Reynosa, Tamaulipas, México.
> (899)9243627 ext. 87747
> e-mail: asegurac at ipn.mx <mailto:asegurac at ipn.mx>; aldosegura at gmail.com 
> <mailto:aldosegura at gmail.com>
> =========================================/*


Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080


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